Mutation ages and population origins inferred from genomes in structured populations

Abstract Inferring the time of origin (age) of mutations is an old question in population genetics and inferring their population of origin has become of particular interest with the sequencing of the Neanderthal genome. However, existing methods to infer mutation ages and populations of origin do not explicitly consider population structure, migration rates, and divergence times, which may bias estimates, and it is unclear how to even apply single-population estimators to structured populations. We develop a method to jointly estimate the time and population of origin of a mutation (as well as the ancestral and derived states) in a structured population using population genomic data and examine its statistical performance using simulations. Results indicate that mutation age and population of origin can be quite uncertain, even with long sequences or many samples, but this uncertainty is accurately captured using credible intervals/sets. The ancestral nucleotide state is relatively easy to infer. We apply our method to whole genome data from the 1000 Genomes Project, analyzing seven SNP mutations from six genes associated with human skin pigmentation for populations from Great Britain, China, and Kenya. Our results partially support previous conclusions, with the putative ancestral alleles from the literature matching our inferences, while the mutation age estimates only overlap in some cases. Furthermore, there are non-trivial posterior probabilities of recurrence for three of the mutations.